title: Peroxisome proliferator-activated receptor-γ activators monascin and rosiglitazone attenuate carboxymethyllysine-induced fibrosis in hepatic stellate cells through regulating the oxidative stress pathway but independent of the receptor for advanced glycation end products signaling.
abstract: Advanced glycation end products (AGEs) signaling through its receptors (RAGE) results in an increase in reactive oxygen species (ROS) and is thought to contribute to hepatic fibrosis via hyperglycemia. Carboxymethyllysine (CML) is a key AGE, with highly reactive dicarbonyl metabolites. We investigated the inhibitory effect of Monascus -fermented metabolite monascin and rosiglitazone on CML-induced RAGE signaling in hepatic stellate cells (HSCs) and its resulting antihepatic fibrosis activity. We found that monascin and rosiglitazone upregulated peroxisome proliferator-activated receptor-γ (PPAR-γ) to attenuate α-smooth muscle actin (SMA) and ROS generation in CML-treated HSCs in a RAGE activation-independent pathway. Therefore, monascin may delay or inhibit the progression of liver fibrosis through the activation of PPAR-γ and might prove to be a major antifibrotic mechanism to prevent liver disease.
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Wei-Hsuan
authors.initials: WH
authors.lastname: Hsu
authors.forename: Bao-Hong
authors.initials: BH
authors.lastname: Lee
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Hsu
authors.forename: Tzu-Ming
authors.initials: TM
authors.lastname: Pan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002478:Cells, Cultured; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000473:pathology; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology*; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000517:prevention & control; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D047495:PPAR gamma / Q000187:drug effects / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000502:physiology; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects; D045162:Thiazolidinediones / Q000494:pharmacology*; D014162:Transfection; D047071:beta-Glucans
chemical_list: D000893:Anti-Inflammatory Agents; D006575:Heterocyclic Compounds, 3-Ring; D047495:PPAR gamma; D034741:RNA, Small Interfering; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D045162:Thiazolidinediones; D047071:beta-Glucans; C516584:micellapist; D000077154:Rosiglitazone; C048496:N(6)-carboxymethyllysine; D008239:Lysine; C517880:monascin